In treating a disease, a carrier is required for introducing a useful substance such as a medicament and a physiologically active substance (hormone and lymphokine and the like) into a cell of a target tissue. Recently, with a progress of technology such as gene therapy and an antisense medical drug, development of a carrier has been aggressively made for efficiently introducing a specific gene and nucleic acid into a cell of a target tissue, particularly, in the field of cancer treatment and the like, the carrier has attracted attention as a novel therapy that may take the place of chemotherapy.
As a method for introducing a gene and a nucleic acid, (1) a viral vector method using a virus and (2) a method of using a non-viral vector such as a lipid membrane structure represented by a liposome are known.
In the former method, although the introduction efficiency thereof is high; however, the risk that viruses (adenovirus, herpes virus, vaccinia virus and RNA viruses such as retro virus) may cause cancer is pointed out as a problem. In addition, it is difficult to produce a large amount of viral vector. Antigenicity and toxicity to a host are also problems. These problems are causes of delaying practical application of gene therapy and the like, by the viral vector method.
In the latter method, Lipofectamine, Lipofectace, Lipofectin, Transfectam and Gene Transfer and the like are commercially available as cationized liposomes for Gene/nucleic acid introducing reagents. By use of these gene/nucleic acid introducing reagents, a gene and a nucleic acid can be introduced into culture cells. However, these gene/nucleic acid introducing reagents have drawbacks such as (a) poor stability of a lipid contained in a reagent, (b) unstable in the presence of the serum, (c) strong cytotoxicity and (d) need to further improve a gene/nucleic acid introduction efficiency into a cell. Because of the drawbacks, the gene/nucleic acid introducing reagents are not satisfactory as therapeutic drugs for gene therapy or nucleic acid medical drug treatment in humans or as reagents for introducing a gene/nucleic acid into animals by direct administration.
To introduce a gene/nucleic acid in vivo, it is desired to apply a gene/nucleic acid introducing reagent, which is a non-viral vector having less interaction with blood components, excellent stability, toxicity and pharmacokinetics and the like, as well as having more excellent introduction efficiency of a gene and a nucleic acid into a cell.
The problem to be solved by the present invention is to provide lipid membrane structures (a liposome, an emulsion and a micelle and the like) having further excellent gene/nucleic acid introduction efficiency and provide novel phospholipid derivatives useful as a main component of the lipid membrane structure.